Comparative Evaluation of subarachnoid block with low dose bupivacaine and fentanyl Vs Low dose bupivacaine and Sufentanil in patients undergoing inguinal surgeries

INTRODUCTION: Spinal anaesthesia is widely used for surgeries involving the lower limb, perineum and inguinal region. The duration of spinal anaesthesia that is timed according to the duration of surgery may help prevent complications associated with prolonged immobilization especially in elderly patients. Recently there has been an interest in using analgesics and local anaesthetics in an attempt to decrease the local anaesthetic dose enabling faster recovery while improving anaesthetic success and providing effective post operative analgesia. The use of intrathecal lignocaine for spinal anaesthesia has been questioned because of the frequent occurrence of Transient Neurological Symptoms. An increasing number of surgeries being performed in the ambulatory setting under spinal anaesthesia has generated interest in finding alternative drugs that would provide adequate surgical anaesthesia while having quick recovery profile and low side effect profile. The discovery of opioid receptors has opened new horizons in pain management. Since their introduction into clinical practice in 1979, spinal opioids have achieved great international popularity in a variety of clinical settings either as sole analgesic agents or in combination with low-dose local anesthetic agents. By bypassing blood and the blood-brain barrier, small doses of opioids administered in either the subarachnoid or epidural spaces provide profound and prolonged segmental analgesia. Numerous studies have shown that spinal opioids can provide profound postoperative analgesia with less central and systemic adverse effects than can opioids administered systematically. Several reviews have appeared in the literature. The rationale for the combination technique is that opioids and local agents eliminate pain by acting at two distinct sites—the local anaesthetic at the nerve axon and the opioid at the receptor site in the spinal cord. If even an extremely low concentration of local anaesthetic is added to the opioid, the quality of analgesia may be far superior. This study thus was designed to test the hypothesis that adding an opioid to the local anaesthetic in the subarachnoid space provides great advantages as has been reported extensively in literature. AIM OF THE STUDY: To study the effect of Low dose Hyperbaric Bupivacaine 10 mg with 5 μg of Sufentanil Vs. Low dose Hyperbaric Bupivacaine 10 mg with 50 μg of Fentanyl on: 1. Block characteristics, 2. Hemodynamic changes. MATERIALS AND METHODS: This study was conducted at Government General Hospital, Madras Medical College and Research Institute, Chennai – 600 003 between July 2006 to August 2006 on 50 patients of ASA Physical Status I and II undergoing Inguinal and below Inguinal region surgeries. The study was done after getting institutional approval. Written informed consent was obtained from all patients included in the study. Study Design: This study was done in a prospective double blind randomized manner. The patients were divided into two groups of twenty-five each . Patient meeting criteria incorporated into study, randomly allotted to either group by draw of lots. Group F: Patients in this group received 10 mg of 0.5% hyperbaric bupivacaine with 50 μg of Fentanyl added to a total volume of 3 ml. Group S: Patients in this group received 2 ml [10 mg] of 0.5% hyperbaric bupivacaine with sufentanil 5 μg [diluted with 5% dextrose] and volume made to 3 ml. The final volume of injected solutions was 3 ml in both the groups. In the study 0.5% Bupivacaine in 8% dextrose manufactured by SPM Drugs, Fentanyl citrate [Free] manufactured by PHARMACHEMICO laboratories, sufentanil manufactured by CORE HEALTH and the dilutent 5% dextrose prepared by IVES DRUG INDIA LTD was used. All solutions were prepared under aseptic precaution by the operation theatre incharge anaesthesiologist uninvolved in the administration of subarachnoid block or in the observation of patients. The specific gravity of the injected solution 1.008 and this was hyperbaric related to cerebrospinal fluid [1.006]. Selection of Cases: Inclusion Criteria: 1. Male and female patients in age group of 20-60 years undergoing elective Inguinal and below Inguinal region surgeries. 2. ASA I and II. Exclusion Criteria: 1. Patient’s refusal. 2. ASA physical status III, IV and V. 3. Deformity of vertebral column. 4. Neurological diseases. 5. Local sepsis. 6. Bleeding diathesis. Following observation were made: 1. Intrathecal opioids [either Fentanyl or sufentanil] in combination with low doses of local anaesthetic [10 mg of 0.5% bupivacaine] produced satisfactory sensory block of the lower abdomen. 2. The onset of sensory block was little earlier when bupivacaine was combined with sufentanil [7.4 min] than fentanyl [9.04 min]. 3. The mean duration of sensory block was almost the same when bupivacaine was either combined with fentanyl [142.8 min] or sufentanil [137.8 min]. 4. The mean duration of analgesia was significantly longer with bupivacaine combined with sufentanil [264.6 min] than with fentanyl 216.8. 5. The mean duration of motor block was shorter with sufentanil in combination with bupivacaine [90.8 min] than fentanyl-bupivacaine combination [131.6 min]. 6. The variation of heart rate, systolic blood pressure and diastolic blood pressure from the baseline in both the groups was not statistically significant establishing a hemodynamic stability of intrathecal opioid low dose local anaesthetic combination than intrathecal local anaesthetic alone. 7. The incidence of side effects was relatively low with both the combination with only pruritis emerging as the leading complication in the either of the groups. 8. The percentage of cases reporting nausea, vomiting was very few in either of the groups. 9. None of the cases in either of the groups was complicated by respiratory depression, sedation and urinary retention. 10.No neurological complication were observed in any of the patients. CONCLUSION: This study confirms the safety and efficacy of intrathecal low dose local anaesthetic opioid combination in patients undergoing surgeries of inguinal region region of intermediate duration. When compared to intrathecal bupivacaine fentanyl combination; intrathecal bupivacaine sufentanil combination provided prolonged post operative analgesia with a lesser duration of motor blockade thus allowing early post operative ambulation. Both the groups were comparable with regards to haemodynamic stability. The side effects of intrathecal opioids are not significant and can be easily managed

Power Quality Enhancement of Grid interconnected wind energy system with 4-Leg Inverter

A Power quality problem is an occurrence of nonstandard voltage, current or frequency that results in a failure or a misoperation of end user equipments. Utility distribution networks, sensitive industrial loads and critical commercial operations suffer from various types of outages and service interruptions which can cost significant financial losses.With the increase in load demand, the Renewable Energy Sources (RES) are increasingly connected in the distribution systems which utilizes power electronic Converters/Inverters. This paper presents a novel control strategy for achieving maximum benefits from these grid-interfacing inverters using the closed loop fuzzy logic control, when installed in 3-phase 4-wire distribution systems. The inverter is controlled to perform as a multi-function device by incorporating active power filter functionality. The inverter can thus be utilized as: 1) power converter to inject power generated from RES to the grid, and 2) shunt APF to compensate current unbalance, load current harmonics, load reactive power demand and load neutral current. All of these functions may be accomplished either individually or simultaneously. This new control concept is demonstrated with extensive MATLAB/Simulink. Index Terms—Active power filter (APF), distributed generation (DG), distribution system, grid interconnection, power quality (PQ), renewable energy, Photo Voltaic (PV) System

Secrecy Sustain Broadcast Assessment for Collective Information in Cloud Computing

Cloud computing could be a mode of method that shares computing resources considerably than enclose native servers or personal devices to regulate productions. Cloud information storage has varied compensations over native info storage. Client will transmit their info on cloud and retrieve those uploaded information from anytime and anyplace with none further burden. It condenses value by assign computing and tortuous, storage resources with associate on command provisioning mechanism counting on a forfeit use business type. The User doesn’t ought to agonize concerning storage and maintenance of cloud information. because the information is keep at the isolated place however users can get the confirmation a propos keep information. thence Cloud information storage ought to have some procedure which is able to detail storage correctness and integrity of data keep on cloud. Users will resort to a third-party auditor (TPA) to ascertain the honesty of outsourced information and be agonize gratis. TPA ought to be ready to competently audit the cloud information storage exclusive of difficult the native copy of data. Specifically, our involvement during this work are often potted because the following aspects: Stimulate the Public     Auditing procedure of information storage safety in Cloud Computing and supply a privacy conserving auditing rule, i.e., our proposal supports associate exterior auditor to audit user’s outsourced info within the cloud while not learning info on the info gist. In difficult, our theme accomplish batch auditing wherever many delegated auditing trip from completely different users are often execute at the same time by the TPA

Chemoattractant Receptors Activate Distinct Pathways for Chemotaxis and Secretion. Role of G-Protein Usage

Human leukocyte chemoattractant receptors activate chemotactic and cytotoxic pathways to varying degrees and also activate different G-proteins depending on the receptor and the cell-type. To determine the relationship between G-protein usage and the biological and biochemical responses activated, receptors for the chemoattractants formyl peptides (FR), platelet- activating factor (PAFR), and leukotriene B4 (BLTR) were transfected into RBL-2H3 cells. Pertussis toxin (Ptx) served as a Gα(i) inhibitor. These receptors were chosen to represent the spectrum of G(i) usage as Ptx had differential effects on their ability to induce calcium mobilization, phosphoinositide hydrolysis, and exocytosis with complete inhibition of all responses by FR, intermediate effects on BLTR, and little effect on PAFR. Ptx did not affect ligand-induced phosphorylation of PAFR and BLTR but inhibited phosphorylation of FR. In contrast, chemotaxis to formylmethionylleucylphenylalanine, leukotriene B4, and platelet-activating factor was completely blocked by Ptx. Wortmannin, a phosphotidylinositol 3- kinase inhibitor, also completely blocked ligand-induced chemotaxis by all receptors but did not affect calcium mobilization or phosphoinositide hydrolysis; however, it partially blocked the exocytosis response to formylmethionylleucylphenylalanine and the platelet-activating factor. Membrane ruffling and pseudopod extension via the BLTR was also completely inhibited by both Ptx and wortmannin. These data suggest that of the chemoattractant receptors studied, G-protein usage varies with FR being totally dependent on G(i), whereas BLTR and PAFR utilize both G(i) and a Ptx- insensitive G-protein. Both Ptx-sensitive and -insensitive G-protein usage can mediate the activation of phospholipase C, mobilization of intracellular calcium, and exocytosis by chemoattractant receptors. Chemotaxis, however, had an absolute requirement for a G(i)-mediated pathway

Fuzzy logic controller based DC-Link Voltage Self-Balance Method for Multilevel Converter with less Number of Voltage Sensors

In many inverters, Voltage balance of dc-link capacitors is very important for applications of a cascade multilevel converter or a modular multilevel converter. In this paper, a novel diode-clamped modular multilevel converter (DCM2 C) topology is proposed and a power feedback control method is developed with fuzzy logic controller. With the developed control strategy, the proposed diode-clamped circuit becomes controllable closed loop which enables the capacitor voltages to be clamped by low power rating clamping diodes. The proposed topology and control strategy has quicker response with transient state error reduction and requires much fewer voltage sensors than the normally used traditional method of multilevel inverters as diode clamped inverters; therefore, the system performance improvement and cost reduction are expected. Based on the proposed DCM2 C, a novel N +1-level cascade multilevel topology is proposed for a cascade active power filter (CS-APF). The Proposed fuzzy logic controller is implemented to get study state response at dc voltage capacitors, therefore to get balanced load outputs. The simulation results from the CS-APF have demonstrated and verified the effectiveness of the proposed novel topology and control method

N-acetyltransferase gene polymorphisms & plasma isoniazid concentrations in patients with tuberculosis

Background & objectives: Variations in the N-acetyltransferase (NAT2) gene among different populations could affect the metabolism and disposition of isoniazid (INH). This study was performed to genotype NAT2 gene polymorphisms in tuberculosis (TB) patients from Chennai, India, and compare plasma INH concentrations among the different genotypes. Methods: Adult patients with TB treated in the Revised National TB Control Programme (RNTCP) in Chennai, Tamil Nadu, were genotyped for NAT2 gene polymorphism, and two-hour post-dosing INH concentrations were compared between the different genotypes. Plasma INH was determined by high-performance liquid chromatography. Genotyping of the NAT2 gene polymorphism was performed by real-time polymerase chain reaction method. Results: Among the 326 patients genotyped, there were 189 (58%), 114 (35%) and 23 (7%) slow, intermediate and fast acetylators, respectively. The median two-hour INH concentrations in slow, intermediate and fast acetylators were 10.2, 8.1 and 4.1 μg/ml, respectively. The differences in INH concentrations among the three genotypes were significant (P<0.001). Interpretation & conclusions: Genotyping of TB patients from south India for NAT2 gene polymorphism revealed that 58 per cent of the study population comprised slow acetylators. Two-hour INH concentrations differed significantly among the three genotypes

An Essential Role of the Cytoplasmic Tail of CXCR4 in G-Protein Signaling and Organogenesis

CXCR4 regulates cell proliferation, enhances cell survival and induces chemotaxis, yet molecular mechanisms underlying its signaling remain elusive. Like all other G-protein coupled receptors (GPCRs), CXCR4 delivers signals through G-protein-dependent and -independent pathways, the latter involving its serine-rich cytoplasmic tail. To evaluate the signaling and biological contribution of this G-protein-independent pathway, we generated mutant mice that express cytoplasmic tail-truncated CXCR4 (ΔT) by a gene knock-in approach. We found that ΔT mice exhibited multiple developmental defects, with not only G-protein-independent but also G-protein-dependent signaling events completely abolished, despite ΔT's ability to still associate with G-proteins. These results reveal an essential positive regulatory role of the cytoplasmic tail in CXCR4 signaling and suggest the tail is crucial for mediating G-protein activation and initiating crosstalk between G-protein-dependent and G-protein-independent pathways for correct GPCR signaling

The Chemokine CXCL12 Is Essential for the Clearance of the Filaria Litomosoides sigmodontis in Resistant Mice

Litomosoides sigmodontis is a cause of filarial infection in rodents. Once infective larvae overcome the skin barrier, they enter the lymphatic system and then settle in the pleural cavity, causing soft tissue infection. The outcome of infection depends on the parasite's modulatory ability and also on the immune response of the infected host, which is influenced by its genetic background. The goal of this study was to determine whether host factors such as the chemokine axis CXCL12/CXCR4, which notably participates in the control of immune surveillance, can influence the outcome of the infection. We therefore set up comparative analyses of subcutaneous infection by L. sigmodontis in two inbred mouse strains with different outcomes: one susceptible strain (BALB/c) and one resistant strain (C57BL/6). We showed that rapid parasite clearance was associated with a L. sigmodontis-specific CXCL12-dependent cell response in C57BL/6 mice. CXCL12 was produced mainly by pleural mesothelial cells during infection. Conversely, the delayed parasite clearance in BALB/c mice was neither associated with an increase in CXCL12 levels nor with cell influx into the pleural cavity. Remarkably, interfering with the CXCL12/CXCR4 axis in both strains of mice delayed filarial development, as evidenced by the postponement of the fourth molting process. Furthermore, the in vitro growth of stage 4 filariae was favored by the addition of low amounts of CXCL12. The CXCL12/CXCR4 axis thus appears to have a dual effect on the L. sigmodontis life cycle: by acting as a host-cell restriction factor for infection, and as a growth factor for worms

A community effort in SARS-CoV-2 drug discovery.

peer reviewedThe COVID-19 pandemic continues to pose a substantial threat to human lives and is likely to do so for years to come. Despite the availability of vaccines, searching for efficient small-molecule drugs that are widely available, including in low- and middle-income countries, is an ongoing challenge. In this work, we report the results of an open science community effort, the "Billion molecules against Covid-19 challenge", to identify small-molecule inhibitors against SARS-CoV-2 or relevant human receptors. Participating teams used a wide variety of computational methods to screen a minimum of 1 billion virtual molecules against 6 protein targets. Overall, 31 teams participated, and they suggested a total of 639,024 molecules, which were subsequently ranked to find 'consensus compounds'. The organizing team coordinated with various contract research organizations (CROs) and collaborating institutions to synthesize and test 878 compounds for biological activity against proteases (Nsp5, Nsp3, TMPRSS2), nucleocapsid N, RdRP (only the Nsp12 domain), and (alpha) spike protein S. Overall, 27 compounds with weak inhibition/binding were experimentally identified by binding-, cleavage-, and/or viral suppression assays and are presented here. Open science approaches such as the one presented here contribute to the knowledge base of future drug discovery efforts in finding better SARS-CoV-2 treatments.R-AGR-3826 - COVID19-14715687-CovScreen (01/06/2020 - 31/01/2021) - GLAAB Enric